, Volume 41, Issue 2, pp 667–676 | Cite as

Deficiency of IL-18 Aggravates Esophageal Carcinoma Through Inhibiting IFN-γ Production by CD8+T Cells and NK Cells

  • Jiantao Li
  • Gang Qiu
  • Baoshuan Fang
  • Xiaohui Dai
  • Jianhui Cai


To investigate the potential role of interleukin-18 (IL-18) in immunomodulation during tumorigenesis of esophageal carcinoma and elucidate the underlying molecular mechanism, we employed IL-18 knockout mice for this purpose. Carcinogen 4-nitroquinoline 1-oxide (4NQO) was administrated in drinking water to induce occurrence of esophageal squamous cell carcinoma (ESCC). T cell activation as indicated by the surface CD molecules was analyzed with flow cytometry. The serous content of interferon-γ (IFN-γ) along with other cytokines was determined by inflammatory human cytokine cytometric bead array. The cytotoxicity assay was performed by co-culture of tumor cells with immune cells and relative cell viability was determined by lactate dehydrogenase (LDH) assay. Apoptotic cells were stained with Annexin-V/propidium iodide (PI) and analyzed by flow cytometry. Cell proliferation was measured with Cell Counting Kit-8 (CCK-8) assay. Our data demonstrated that deficiency of IL-18 promoted the progression and development of 4NQO-induced ESCC. Loss of IL-18 suppressed the activation of T cells in the esophagus. Deficiency of IL-18 inhibited the IFN-γ production by CD8+ T cells and natural killer (NK) cells. Absence of IL-18 inhibited the cytotoxicity of CD8+ T cells and NK cell in vitro. Moreover, deficiency of IL-18 promoted the apoptosis of CD8+ T cells and inhibited the proliferation of CD8+ T cells in vitro. Our data elucidated the immunomodulatory role of IL-18 during tumorigenesis of ESCC, whose deficiency compromised antitumor immunity and contributed to immune escape of esophageal carcinoma. Our results also indicated the therapeutic potential of exogenous IL-18 against ESCC, which warrants further investigations.

Key Words

Esophageal carcinoma IL-18 IFN-γ CD8+ T cell Apoptosis 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Research Involving Human Participants and/or Animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed Consent

Not applicable.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Jiantao Li
    • 1
    • 2
  • Gang Qiu
    • 2
  • Baoshuan Fang
    • 2
  • Xiaohui Dai
    • 1
  • Jianhui Cai
    • 1
  1. 1.Hebei Medical UniversityShijiazhuangChina
  2. 2.Hebei General HospitalShijiazhuangChina

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